The broad long-term objective of this proposal is to understand why memory loss occurs in Alzheimer's disease. The more immediate objective of our research is to investigate the hypothesis that the beta-amyloid molecule (AFJ) has dual roles in learning and memory, one beneficial and the other harmful. We have developed transgenic mice expressing various forms of the amyloid precursor protein that show either superior memory or an age-related deterioration in memory. We have shown that monomeric AB is present from infancy in neurons of the brain, but that abnormal, aggregated forms of AI_ appear only with aging. We propose to determine whether there is a normal form of AB, called AB*, which enhances memory. We have evidence that abnormal forms of AB are associated with memory loss, and propose to further delineate the corresponding AI3 species, called AB*.